Refractive errors (myopia and hyperopia) are the most widespread human eye disorders. By the year 2020, one third of the world's population-over 2.5 billion people-will be affected by myopia alone. The global economic productivity loss from uncorrected refractive errors has been estimated to be $268 billion. Hence, refractive errors are a significant Public Health problem, especially in regions of East Asia where myopia has reached epidemic proportions. Refractive errors are complex traits, in which both inherited genetic and environmental/behavioral factors are thought to play significant roles. The objective of this project is to study the effects of gene-environment interactions on ocular refraction within the context of whole-genome association studies. The proposed research will make use of 6 large datasets from genomic studies conducted in the United States, Germany, and Singapore. Our specific aims are to: 1) discover of genetic polymorphisms which interact with environmental factors in gene-environment-wide interaction studies of refractive error; and 2) identify biological pathways or gene-sets through which environmental factors mediate refractive error development in humans. The ultimate goals of the research are to better understand the complex biology of ocular refractive development, and identify specific genes which interact with environmental factors (as measured by proxies of exposure to high visual demand, such as education and reading) in refractive error. The proposed research is part of a K08 Mentored Clinical Scientist Research Career Development Award. Training in the grant period will focus on developing skills necessary in the design, management, analysis and interpretation of large-scale gene-environment-wide studies. Dr. Wojciechowski's long-term career will be devoted to translating the vast data provided by large genomic studies into clinically useful, comprehensible, and practical information. This information will ultimately benefit scientists, clinicians, Public Health practitioners, policy makers and, most importantly, the public at large.